Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis.
Association of Cortical Lesion Burden on 7-T Magnetic Resonance Imaging With Cognition and Disability in Multiple Sclerosis.
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DOI：
10.1001/jamaneurol.2015.1241
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发表时间：
2015-09
期刊：
影响因子：
29
通讯作者：
Calabresi PA
中科院分区：
文献类型：
--
作者：
Harrison DM;Roy S;Oh J;Izbudak I;Pham D;Courtney S;Caffo B;Jones CK;van Zijl P;Calabresi PA
皮质病变（CLs）有助于多发性硬化症（MS）的身体和认知障碍。为了评估高场磁共振成像（MRI）在多发性硬化症中的临床相关性，在一个学术多发性硬化症中心进行了一项观察性临床影像学研究。参与者包括36名MS患者（30名复发缓解型，6名继发性或原发性进展型）和15名健康个体作为对照。研究时间为2010年3月10日至2012年11月23日，分析时间为2011年6月1日至2014年9月30日。采用0.5 mm各向同性分辨率磁化制备的快速采集梯度回波（MPRAGE）和全脑、三维、1.0 mm各向同性分辨率磁化制备的流体衰减反演恢复（MPFLAIR）对脑部进行7特斯拉MRI。在MPRAGE上显示为低信号的皮质病变被手工分割。病变分为脑白质、脑皮层内和脑皮层下。使用病变- toads（拓扑保留解剖分割）算法对图像进行分割，并报告脑结构体积和白质（WM）病变体积。体积归一化为颅内体积。身体残疾采用扩展残疾状态量表（EDSS）进行测量。认知功能障碍用MS电池最小认知功能评估法测量。36名参与者中有35名（97%）出现皮质病变，平均每个参与者16个病变（范围0-99）。白质皮层病变体积与WM病变体积相关（ρ = 0.50; P = 0.003），但与皮质体积无关；枕下病变体积与皮质体积呈负相关（ρ = - 0.36; P = .04），但与WM病变体积无关。CL总数和体积,测量值(范围),显著增加了参与者与eds分数为5.0或更对那些分数小于5.0(数:29(11 - 99)对13[0-51];体积:2.81×10−4(1.30×10−4到7.90×10−4]vs 1.50×10−4[0到1.01×10−3])和认知能力受损vs unim-paired个人(数:21(0 - 99)对13[1-54];体积:3.51×10−4[0到1.01×10−4]vs 1.19×10−4[0到7.17×10−4])。皮层病变体积与EDSS评分的相关性强于WM病变体积（ρ = 0.59 vs 0.36）。在调整年龄和性别后，增加log[CL体积]使认知障碍的几率增加3倍（优势比[OR]， 3.36; 95% CI, 1.07-10.59; P = 0.04），在调整WM病变体积和萎缩后，使认知障碍的几率增加14倍（OR, 14.26; 95% CI, 1.06-192.37; P = 0.045）。白质皮质病变对认知的影响最大（对数[白质皮质病变体积]的OR为9.65；95% CI为1.70-54.59,P = 0.01）。这项研究提供了活体证据，证明CLs与MS患者的认知和身体残疾有关，并且白细胞皮质和枕下病变亚型具有不同的临床相关性。高场MRI对CL负担的定量评估可能会进一步加深我们对MS的残疾发展和进展的理解，并导致更有效的治疗。
Cortical lesions (CLs) contribute to physical and cognitive disability in multiple sclerosis (MS). Accurate methods for visualization of CLs are necessary for future clinical studies and therapeutic trials in MS. To evaluate the clinical relevance of measures of CL burden derived from high-field magnetic resonance imaging (MRI) in MS. An observational clinical imaging study was conducted at an academic MS center. Participants included 36 individuals with MS (30 relapsing-remitting, 6 secondary or primary progressive) and 15 healthy individuals serving as controls. The study was conducted from March 10, 2010, to November 23, 2012, and analysis was performed from June 1, 2011, to September 30, 2014. Seven-Tesla MRI of the brain was performed with 0.5-mm isotropic resolution magnetization-prepared rapid acquisition gradient echo (MPRAGE) and whole-brain, 3-dimensional, 1.0-mm isotropic resolution magnetization–prepared, fluid-attenuated inversion recovery (MPFLAIR). Cortical lesions, seen as hypointensities on MPRAGE, were manually segmented. Lesions were classified as leukocortical, intracortical, or subpial. Images were segmented using the Lesion-TOADS (Topology-Preserving Anatomical Segmentation) algorithm, and brain structure volumes and white matter (WM) lesion volume were reported. Volumes were normalized to intracranial volume. Physical disability was measured by the Expanded Disability Status Scale (EDSS). Cognitive disability was measured with the Minimal Assessment of Cognitive Function in MS battery. Cortical lesions were noted in 35 of 36 participants (97%), with a median of 16 lesions per participant (range, 0-99). Leukocortical lesion volume correlated with WM lesion volume (ρ = 0.50; P = .003) but not with cortical volume; subpial lesion volume inversely correlated with cortical volume (ρ = −0.36; P = .04) but not with WM lesion volume. Total CL count and volume, measured as median (range), were significantly increased in participants with EDSS scores of 5.0 or more vs those with scores less than 5.0 (count: 29 [11-99] vs 13 [0-51]; volume: 2.81 × 10−4 [1.30 × 10−4 to 7.90 × 10−4] vs 1.50 × 10−4 [0 to 1.01 × 10−3]) and in cognitively impaired vs unim-paired individuals (count: 21 [0-99] vs 13 [1-54]; volume: 3.51 × 10−4 [0 to 1.01 × 10−4] vs 1.19 × 10−4 [0 to 7.17 × 10−4]). Cortical lesion volume correlated with EDSS scores more robustly than did WM lesion volume (ρ = 0.59 vs 0.36). Increasing log[CL volume] conferred a 3-fold increase in the odds of cognitive impairment (odds ratio [OR], 3.36; 95% CI, 1.07-10.59; P = .04) after adjustment for age and sex and a 14-fold increase in odds after adjustment for WM lesion volume and atrophy (OR, 14.26; 95% CI, 1.06-192.37; P = .045). Leukocortical lesions had the greatest effect on cognition (OR for log [leukocortical lesion volume], 9.65; 95% CI, 1.70-54.59, P = .01). This study provides in vivo evidence that CLs are associated with cognitive and physical disability in MS and that leukocortical and subpial lesion subtypes have differing clinical relevance. Quantitative assessments of CL burden on high-field MRI may further our understanding of the development of disability and progression in MS and lead to more effective treatments.